Production of polymeric micelles by microfluidic technology for combined drug delivery: Application to osteogenic differentiation of human periodontal ligament mesenchymal stem cells (hPDLSCs)

被引:29
作者
Capretto, L. [1 ]
Mazzitelli, S.
Colombo, G.
Piva, R. [2 ]
Penolazzi, L. [2 ]
Vecchiatini, R. [2 ]
Zhang, X. [1 ]
Nastruzzi, C.
机构
[1] Univ Southampton, Fac Engn & Environm, Southampton SO17 1BJ, Hants, England
[2] Univ Ferrara, Dept Biochem & Mol Biol, I-44100 Ferrara, Italy
基金
英国工程与自然科学研究理事会;
关键词
Microfluidics; Lab-on-a-chip; Osteogenic differentiation; Human periodontal ligament mesenchymal stem cells; IN-VITRO; BLOCK-COPOLYMERS; PARTICLE-SIZE; SOLUBILIZATION; CYTOMETER; MARROW; GROWTH; NICHE;
D O I
10.1016/j.ijpharm.2012.07.057
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The current paper reports the production of polymeric micelles (PMs), based on pluronic block-copolymers, as drug carriers, precisely controlling the cellular delivery of drugs with various physico-chemical characteristics. PMs were produced with a microfluidic platform to exploit further control on the size characteristic of the PMs. PMs were designed for the co-delivery of dexamethasone (Dex) and ascorbyl-palmitate (AP) to in vitro cultured human periodontal ligament mesenchymal stem cells (hPDLSCs) for the combined induction of osteogenic differentiation. Mixtures of block-copolymers and drugs in organic, water miscible solvent, were conveniently converted in PMs within microfluidic channel leveraging the fast mixing at the microscale. Our results demonstrated that the drugs can be efficiently co-encapsulated in PMs and that different production parameters can be adjusted in order to modulate the PM characteristics. The comparative analysis of PM produced by microfluidic and conventional procedures confirmed that the use of microfluidics platforms allowed the production of PMs in a robust manner with improved controllability, reproducibility, smaller size and polydispersity. Finally, the analysis of the effect of PMs, containing Dex and AP, on the osteogenic differentiation of hPDLSCs is reported. The data demonstrated the effectiveness and safety of PM treatment on hPDLSC. In conclusion, this report indicates that microfluidic approach represents an innovative and useful method for PM controlled preparation, warrant further evaluation as general methodology for the production of colloidal systems for the simultaneous drug delivery. (c) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:195 / 206
页数:12
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